Additional CREST data shed light on imAEs with sasanlimab plus BCG

Treatment with sasanlimab plus BCG was associated with a manageable immune-mediated adverse event (imAE) profile in patients with high-risk, BCG-naïve non–muscle invasive bladder cancer (NMIBC), according to data presented at the 2025 European Society for Medical Oncology Congress in Berlin, Germany.¹

The findings were obtained from the phase 3 CREST trial (NCT04165317), which previously demonstrated that the combination of sasanlimab plus BCG significantly extended event-free survival vs BCG alone in this patient population (HR, 0.68; 95% CI, 0.49 to 0.94; 2-sided P = .019), with a manageable safety profile.

In total, the CREST trial enrolled 1055 patients. For the study, patients were randomly assigned 1:1:1 to receive sasanlimab plus BCG induction plus maintenance (n = 350; BCG-I+M), sasanlimab plus BCG induction (n = 348; BCG-I), or BCG induction and maintenance alone (n = 357).

Data from this subsequent analysis of the trial showed that the rate of imAEs were similar between both sasanlimab plus BCG arms, with an incidence of any-grade imAEs of 43% in the sasanlimab plus BCG-I+M arm and 47% in the sasanlimab plus BCG-I arm. Further, the rate of any grade 3 or higher imAE was 16% in the sasanlimab plus BCG-I+M arm vs 14% in the sasanlimab plus BCG-I arm.

When these cohorts were pooled together (n = 698), the rate of any grade imAEs was 45% (312 of 698). Broken down by grade of severity, 9% (n = 64) of patients had a grade 1 imAE, 21% (n = 144) had grade 2, 12% (n = 86) had grade 3, 2% (n = 17) had grade 4, and less than 1% (n = 1) had grade 5. Across both cohorts, 67% (208 of 312) of patients had a grade 1/2 imAE as the highest grade.

According to the authors, led by Jens Bedke, MD, a senior consultant in the Department of Urology & Transplantation Surgery at the Eva Mayr-Stihl Cancer Center Stuttgart, Klinikum Stuttgart in Germany, “The most common any-grade imAEs by clusters were thyroid disorders (19%) and rash (13%). The most common grade ≥3 imAEs by cluster were hepatitis and rash (3% each). The most common imAEs leading to discontinuation of sasanlimab were rash and hepatitis (3% each).”

Other imAEs included adrenal insufficiency (3%), colitis (3%), hypophysitis/hypopituitarism (2%), nephritis and renal dysfunction (2%), pneumonitis (2%), type 1 diabetes (2%), myocarditis (less than 1%), myositis (less than 1%), myasthenic syndrome/myasthenia gravis (less than 1%), and uveitis (less than 1%). imAEs led to sasanlimab discontinuation in 16% of patients and BCG discontinuation in 2% of patients.

Systemic corticosteroids were administered in 45% (139 of 312) of patients who experienced an imAE, of whom 77 received a high dose (≥40 mg daily prednisolone or equivalent). Further, 74% of patients who experienced an immune-mediated thyroid disorder were given hormonal replacement therapy, and all patients with immune-mediated type 1 diabetes required insulin.

As of the data cut-off in December 2024, 40% (n = 125) of patients who experienced an imAEs had all imAEs resolved.

Overall, the authors concluded, “imAEs seen with sasanlimab in combination with BCG were aligned with the known safety profile of ICIs. imAEs were manageable with treatment interruption/discontinuation and administration of corticosteroids and/or hormonal replacement therapy.”

REFERENCES

1. Bedke J, Shore ND, Powles TB, et al. Immune-mediated adverse events (imAEs) associated with sasanlimab in combination with Bacillus Calmette-Guérin (BCG): Phase III study (CREST). Presented at: 2025 European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. Abstract 3078P. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2025_abstracts/3078P.html.pdf

2. Shore ND, Powles T, Bedke J, et al. Sasanlimab in combination with Bacillus Calmette-Guérin improves event-free survival versus Bacillus Calmette Guérin as standard of care in high-risk non-muscle invasive bladder cancer: Phase 3 CREST study results. J Urol. 2025;213(5S)